Particulate matter (PM) attributable to traffic and other combustion sources has been associated with cardiac- related health outcomes, respiratory disease, lung cancer, and overall mortality. Experimental evidence in animals and humans suggests that exposure to traffic-related PM results in systemic inflammation, oxidative stress and cell cycle dysregulation, as well as direct genotoxicity. However, the precise mechanisms are poorly defined and have not been well characterized in large "real-world" populations. We propose to prospectively characterize personal exposures to vehicle exhaust while concurrently collecting repeated blood and urine samples in a subpopulation of the Trucking Industry Particle Study, an ongoing national epidemiologic and exposure assessment study. We will assess relationships between measured exposures and biomarkers of exposure and oxidative and inflammatory effects. Specifically we will measure serum levels of 1, 2 naphthoquinone and 1, 4-naphthoquinone albumin adducts and urinary naphthols (biomarkers of traffic- related exposure) and serum levels of C-reactive protein, interleukin-6 and soluble intercellular adhesion molecule-1 and urine levels of 8-hydroxy-2'-deoxyguanosine (biomarkers of effect) with concurrent exposure measurements. Exposure measurements will include elemental carbon, naphthalene, and bound polycyclic aromatic hydrocarbons (PAH), a novel specific indicator of PAHs attached to elemental carbon particles that can concentrate and transport them into the target areas of the lungs and internal organs. Finally, we will perform genome-wide gene expression micro array analysis using whole blood RNA to identify genes and gene networks that are differentially activated in response to vehicle exhaust exposure. We anticipate that the results of this project will provide novel and comprehensive insights into the normal biologic response to vehicle exhaust, the relevant etiologic agents of exposure, and will further our understanding of those processes implicated in the development of lung cancer and heart disease. These issues are of great public health importance due to the large proportion of the general population exposed to vehicle exhaust on a daily basis. Furthermore, our proposed aims are consistent with the goals of NIEHS Environmental Genome Project (EGP) to improve understanding of human genetic susceptibility to environmental exposures PUBLIC HEALTH RELEVANCE: Particulate matter (PM) attributable to traffic and other combustion sources has been associated with cardiac- related health outcomes, respiratory disease, lung cancer, and overall mortality. We anticipate that the results of this project will provide novel and comprehensive insights into the normal biologic response to vehicle exhaust, the relevant etiologic agents of exposure, and will further our understanding of those processes implicated in the development of lung cancer and heart disease. These issues are of great public health importance due to the large proportion of the general population exposed to vehicle exhaust on a daily basis.